HIV and Infant Feeding:

1
HIV and Infant Feeding

• Knowledge, Gaps, and Challenges for the Future
• by
• Ellen G. Piwoz
• Jay Ross
• Academy for Educational Development

2
Overview of the Presentation

• Context of the presentation
• Overview of HIV transmission during breastfeeding
  
• risk factors
• timing of transmission
• feasibility of feeding alternatives
• Challenges for the future

3
Timing of Mother-to-Child HIV Transmission with
Breastfeeding and No ARV
Early Antenatal (lt36 wks)
Late Postpartum (6-24 months)
Early Postpartum (0-6 months)
Labor and Delivery
Late Antenatal (36 wks to labor)
5-10
10-20
10-20
Adapted from N Shaffer, CDC
4
MTCT in 100 HIV Mothers by Timing of
Transmission
63 uninfected
15
15
7
5
Major causes of death among children under five,
world, 2000
Deaths associated with undernutrition 60
EIP/WHO Caulfield et al, forthcoming
6
Technical Overview of HIV Transmission during
Breastfeeding
7
Risk Factors For Postnatal Transmission

• Mother
• Immune status
• Plasma viral load
• Breast milk virus
• Breast infection (mastitis, abscess, bleeding
  nipples)
• New HIV infection
• Viral Characteristics

• Infant
• Breastfeeding duration
• Non-exclusive BF
• Age (first months)
• Lesions in mouth, intestine
• Prematurity
• Infant immune response

WHO, 1998 Bulterys et al, 2002 Newell et al,
2002
8
How does HIV transmission during breastfeeding
occur?

• Exact mechanisms unknown
• HIV virus in blood passes to breast milk
• cell-free, cell-associated virus observed
• virus shed intermittently (undetectable 25-35)
• levels vary between breasts in samples taken at
  same time (Willumsen et al, 2001)
• Infant consumes HIV
• enters/infects through permeable mucosal
  surfaces, lymphoid tissues, lesions in mouth,
  intestine
• Although BF infant may consume gt500,000 virons,
  gt25,000 infected cells per day, majority dont
  become infected (Lewis et al, 2001)
• immune factors in BM may play a role (Sabbaj et
  al, 2002)

9
Risk factors for postnatal transmission Maternal
immune status
Leroy et al 2002
10
Risk factors for postnatal transmission Maternal
viral load

• Viral RNA is an important predictor of
  intra-partum MTCT (Leroy et al, 2001 Semba et
  al, 1999 Thea et al, 1997)
• Plasma viral load may also be a risk factor
  during breastfeeding
• 29 transmission risk among women infected
  postnatally (Dunn et al, 1992)
• risk of infection after 2 months associated with
  plasma viral load gt 43k copies/ml (John et al,
  2001) (OR2.6)
• predicted MTCT by 12 months, after taking into
  account maternal immune status, Na in breast
  milk (Semba et al, 1999) (Adj OR1.71 log HIV
  load)

11
Risk factors for postnatal transmissionBreast
milk viral load
BM viral load was consistently higher in women
with low CD4 counts (plt0.01). BM RNA was
associated with increased MTCT, after adjusting
for maternal CD4 (OR2.82)
Pillay et al, 2000
12
Prevalence of breast pathologies in HIV women in
Africa

• Mastitis (clinical or sub-clinical)
• Clinical exam 7-11 (Embree, 2000 John et al,
  2001)
• Na/K gt 1.0 11-12 at 6, 14 wk (Willumsen et
  al, 2000)
• Na gt 12 mmol/L 16.4 at 6 wk (Semba et al,
  1999)
• Nipple lesions
• Clinical exam 11-13 (Embree, 2000 John et al,
  2001)
• Clinical exam 10 (Ekpini et al, 1997)
• Hospitalized infants 11 (Kambarami et al, 1997)
• Breast abscesses
• Clinical exam 12 (John et al, 2001)
• Clinical exam 3 (Ekpini et al, 1997)

13
Risk factors for postnatal transmissionBreast
health -1

• Sub-clinical mastitis is associated with higher
  viral load in BM (Willumsen et al, 2000 Semba et
  al, 1999)
• Mastitis is associated with increased risk of
  postnatal transmission
• Kenya (Embree gt 3 mo) OR2.3 (1.1-5.0)
• Kenya (John overall) RR3.9 (1.2-12.7)
• Kenya (John gt2 mo) RR21.8 (2.3-211)
• Malawi (Semba overall) OR2.3 (1.2-4.3)
• Malawi (Semba gt 6 wk) RR3.7 (NS)
• Nipple lesions and breast abscesses also
  associated with increased transmission

14
Risk factors for postnatal transmissionBreast
health -2

• 18-20 of overall MTCT may be attributable to
  mastitis (estimated from mastitis prevalence and
  adjusted risk estimates)
• 18 of all transmission in first year in Malawi
  (Semba et al, 1999)
• 20 of transmission up to 2 years (John et al,
  2001)
• If BF accounts for 40 of all transmission, then
  mastitis (breast health problems) may be the
  cause of 50 all postnatal transmission (20/40)

15
Risk factor for postnatal transmission Duration
of breastfeeding

• Risk of transmission persists for as long as
  breastfeeding is practiced
• Some studies indicate that the risk of HIV
  transmission may be higher in the first 6 months
  of life (Miotti et al, 1999 Nduati et al, 2000
  John et al, 2001)
• Several possible explanations
• higher prevalence of mastitis, breastfeeding
  problems
• infant gut more immature, vulnerable/permeable
• more breast milk consumed

16
Postnatal transmission of HIVDuration of
breastfeeding Ghent meta-analysis -2 (Read et
al, 2002)
Cumulative rates of late postnatal HIV infection
(gt 4 wks)
17
What about HIV transmission during the first
month of breastfeeding?
Monthly Risk of MTCT during Early Breastfeeding
(lt2 months)
18
Postnatal transmission of HIV Pattern of
breastfeeding
Cumulative HIV transmission Durban, SA
Coutsoudis et al, 1999 2001
19
Infant mortality among children born to HIV
mothers by early feeding pattern (0-3 months) in
Harare, Zimbabwe (n2,892) Tavengwa et al, 2002
Adjusted HR for BMNHM vs EBF 5.97 (plt0.001)
Predominant BF vs EBF2.52 (p0.04) Partial BF
vs EBF2.84 (p0.02)
20
Risk factors for postnatal transmission Infant
oral lesions

• Disruption of the skin or mucous membranes in
  mouth and intestine believed to increase the risk
  of HIV transmission during breastfeeding
• epithelial integrity affected by nutritional
  deficiencies, infection
• feeding pattern, mastitis did not effect
  intestinal permeability (Rollins et al, 2001
  Willumsen et al, 2000)
• Infant oral thrush associated with increased risk
  of postnatal transmission
• Kenya OR2.8 (1.3-6.2) (Embree et al, 2000)
• Cote d Ivoire RR5.0 (0.5-39.8) (Ekpini et
  al, 1997)

21
Infant Feeding Options for HIV Mothers
22
WHO recommendations on infant feeding for HIV
women

• When replacement feeding is acceptable,
  feasible, affordable, sustainable and safe,
  avoidance of all breastfeeding by HIV-infected
  mothers is recommended.
• Otherwise, exclusive breastfeeding is
  recommended during the first months of life.
• To minimize HIV transmission risk, breastfeeding
  should be discontinued as soon as feasible,
  taking into account local circumstances, the
  individual womans situation and the risks of
  replacement feeding (including infections other
  than HIV and malnutrition).
• New Data on the Prevention of Mother-to-Child
  Transmission of HIV and their Policy
  Implications Conclusions and Recommendations
  (WHO 2001)

23
How Can Families Decide? -1

• What is meant by ACCEPTABLE?
• There are social and cultural norms about infant
  feeding.
• Concerns about stigma associated women who do not
  breastfeed, suspicion of HIV
• What is meant by FEASIBLE?
• There are economic, behavioral, psycho-social
  aspects for care-giver and infant
• Resources and skills are required

24
How Can Families Decide? -2

• What is meant by SUSTAINABLE?
• It must be practiced every day and night
• Resources must be available throughout
• It should be exclusive over first 6 months
• What is meant by SAFE?
• Free from contamination
• Nutritious
• Free from stigma
• Does not spillover to general population

25
Infants who do not breastfeed have an increased
risk of dying in the first year of life
Pooled Odds Ratios
WHO Collaborative Study Team, 2000
26
Risk of mortality is greater among women without
access to hygiene, sanitation,water
RR of Infant Mortality by Feeding Mode and Health
Environment
Habicht et al., 1988
27
Percent of Total Population with Access to Safe
Water
UNICEF, 2002
28
Percent of Total Population with Access to
Adequate Sanitation
UNICEF, 2002
29
Feeding Options Currently Recommended by WHO
(1998)

• Breastfeeding
• exclusive breastfeeding
• heat-treated breast milk
• wet-nursing
• milks banks
• early cessation of breastfeeding (as soon as
  feasible)

• Replacement feeding
• commercial infant formula
• home prepared infant formula (modified, with
  additional nutrients)
• enriched family diet with BMS/MN supplements
  after 6 months

30
What do we know about the feasibility of
exclusive breastfeeding? (BFHI/MCH/IMCI) -1
infants breastfed exclusively in previous 24
hours
_at_ 3 months
_at_ 5 months
lt 6 months
lt 4 months
31
EBF rates at 6 weeks - over time and after the
introduction of an education and counseling
program on safer breastfeeding practices in
Harare, Zimbabwe (n9,931)
Education and counseling intervention began
ZVITAMBO data
32
Exclusive breastfeeding rates in PMTCT programs
with infant feeding counseling - Barcelona AIDS
abstracts
Methodologies and ages at measurement varied
33
Methods used for measuring exclusive
breastfeeding produce different rate estimates
n970 mothers exposed to infant feeding counseling
ZVITAMBO data
34
What do we know about the feasibility of
early/rapid breastfeeding cessation? -1

• Potential risks for infant
• Dehydration
• Anorexia
• Later behavior problems
• Malnutrition
• Illness or death

• Potential risks for mother
• Engorgement
• Mastitis
• Increased risks of pregnancy
• Depression
• Stigma
• Possible reversion to breastfeeding

Piwoz et al, 2002
35
What do we know about the feasibility of early
breastfeeding cessation? -2 Barcelona AIDS
Conference

• Early, rapid cessation is possible (Uganda,
  Zambia, Botswana)
• Problems encountered
• breast engorgement mastitis babies crying,
  trouble sleeping, appetite loss, diarrhea
  financial constraints with replacement feeding
  family objections
• more problems when cessation lt 6 months
  (Botswana)
• Trained counselors were able to help mothers
  overcome problems
• Provision of replacement feeds, family support
  facilitated process
• Impact on HIV transmission, survival not yet known

36
Breast milk contributes gt 50 of the nutrient
intake of children gt 6 months in developing
countries and wont be easy to replace
Adapted from WHO, 1998 Dewey and Brown, 2002
using data from Bangladesh, Ghana, Guatemala, Peru
37
What do we know about the feasibility of other
breastfeeding options?

• Heat-treated breast milk
• heating milk to 56-62.5 degrees C for 12-15 min
  inactivates HIV in human milk (Jeffreys et al
  2001)
• no data on feasibility of daily use from birth
• may be practical during transition period with
  early cessation
• Use of wet nurse - no data
• monitoring HIV status of wet nurse a challenge
• practice may be less common because of HIV
• Milk banks - no data
• may be feasible in some settings (Brazil, LA
  Region)

38
What do we know about the feasibility of
commercial formula?

• High acceptance/adherence in some countries with
  access to clean water, health care, subsidized
  cost
• Thailand, Brazil, South Africa, Botswana
• Adherence with exclusive use may be higher than
  for exclusive BF (Botswana)
• Stigma associated with its use widely reported in
  Africa
• Access to safe water, health care needed
• Proper instruction on safe preparation, feeding
• Cost - gt 6 months supply

39
Formula use in selected programs where provided
free
Barcelona AIDS Conference
40
Uptake of Infant Formula in PMTCT program sites
in SA
McCoy et al, 2002
41
Evidence of Spillover?Infant feeding patterns in
PMTCT vs.non-PMTCT sites in Botswana (lt 6
months, 24 hr recall)
EBF is lower, mixed feeding is higher in PMTCT
sites
Plt 0.001
MOH/UNICEF, 2002
42
What do we know about the feasibility of home
prepared formula?

• Nutritional adequacy and cost studied in KwaZulu
  Natal, SA
• Fresh and powdered full-cream milk
• Findings
• intakes of vitamins E, C, folic acid, pantothenic
  acid lt 33 of adequate intake (AI)
• intakes of zinc, copper, selenium, vitamin A lt
  80 AI
• intakes of EFA were lt 20-60 AI
• cost was 9.80/month or 20 of average monthly
  income
• preparation time was 20-30 minutes for 120 ml

Papathakis et al, 2002
43
Challenges for the Future

• Policy issues
• Can we reframe the debate on breastfeeding versus
  replacement feeding?
• What is the role of commercial infant formula?
• Implementation
• How do we implement October 2000 guidance/scale
  up?
• Research
• Risk analysis and counseling hampered by
  uncertainty
• Can breastfeeding or replacement feeding be made
  safer for HIV women?
• Learning from ALL our experience

44
Can we reframe our thinking and discussion on
this issue? -1

• Lets talk about improving HIV-free survival
  instead of reducing HIV transmission
• reflects higher objective
• resolves conflicting strategies
• Lets talk about reducing postnatal transmission
  instead of HIV transmission through breastfeeding
• more accurate
• less emotional
• less burdened with the weight of history

45
Can we reframe our thinking and discussion on
this issue? -2

• Focus on maternal health nutrition
• Keeping HIV mothers well may be among the most
  important things we can do to prevent P/N
  transmission
• BF transmission was 2 between 6 w-24 months in
  WA study among women with CD4 gt500 (Leroy et al,
  2002)
• Nutrition depletion, weight loss during BF may
  increase risk of maternal mortality (Nduati et
  al, 2001)
• Keeping mothers alive will improve childs
  chances for survival (Nduati et al, 2001)
• ARV use during BF now being studied

46
Can we make breastfeeding safer for HIV women? -1

• Enhance health/nutrition care for women
• Provide adequate lactation counseling and
  support, involving families/communities
• increase adherence to exclusive breastfeeding
• promote good breastfeeding techniques
• prevent cracked nipples, maintain breast health
• Immediate treatment for mastitis, other systemic
  infections that could affect viral load in BM
• could prevent a sizeable fraction of BF
  transmission
• may be most important in early month(s)

47
Can we make breastfeeding safer for HIV women? -2

• Assist families with early breastfeeding
  cessation
• assess health status of mother and infant
• prepare for the process so that the transition is
  safe (cup-feeding, safe preparation/hygiene,
  stigma)
• heat treat breast milk if weaning is gradual
• could prevent sizeable fraction of BF
  transmission
• Provide adequate nutrition after breastfeeding
  ends
• appropriate breast milk substitutes and/or
  multi-nutrient supplements should be provided to
  prevent malnutrition

48
HIV and Infant Feeding Risk Analysis in Setting
where IMR89/1000 Improving maternal health
safer BF practices
Assumptions 1000 live births 20 prevalence
20 transmission before during delivery,
healthy mother, EBF, lactation management
(SBFHM) reduces postnatal transmission by 67
IMR89/1000
49
HIV and Infant Feeding Risk Analysis in Setting
where IMR100/1000 Improving maternal health
safer BF practices
Assumptions 1000 live births 20 prevalence
20 transmission before during delivery,
healthy mother, EBF, lactation management
(SBFHM) reduces postnatal transmission by 67
50
HIV and Infant Feeding Risk Analysis in Setting
where IMR135/1000 Improving maternal health
safer BF practices
Assumptions 1000 live births 20 prevalence
20 transmission before during delivery,
healthy mother, EBF, lactation management
(SBFHM) reduces postnatal transmission by 67
51
What is the role of commercial formula for
replacement feeding?

• It is the best option for RF if conditions can be
  met
• formulated specially for humans, nutritionally
  fortified
• safe water, access to health care, training in
  safe preparation, feeding required to make it
  safe
• postnatal follow-up also required (monitor
  growth, ensure adequate access/availability)
• cost will make it NOT affordable for poor
  families to purchase
• cost may make it NOT sustainable for governments
• Code of Marketing of BMS protects against misuse
  if enacted/enforced
• But spillover may be unavoidable if BF support
  for HIV-negative and status unknown mothers is
  not adequate

52
Can we make replacement feeding safer for HIV
women?

• Provide safe water environmental conditions
• Family support, community understanding
• Postnatal follow-up and enhanced care
• essential child health interventions
• Screen mothers, target use to those most at risk
• Take measures to prevent unnecessary use of RF
• We must strengthen, not abandon, our efforts to
  support optimal infant feeding for all because of
  HIV. The need is even greater when PMTCT programs
  provide infant formula to HIV women.

53
Thank you